4/8/16: THE HUMAN MICROBIOME: THE SCOURGE OF CLOSTRIDIUM DIFFICILE and the Amazing Transplant Cure

digestivesystem

I had a rude and angry introduction to Clostridium difficile, a bacterium that, according to the U.S. Centers for Disease Control and Prevention, causes almost a half-million infections among U.S. patients each year. “C. diff” is THE most common pathogen in hospital-acquired infections.

Before I even knew C. diff existed—much less learned how widespread it is—my father contracted this nasty intestinal infection, characterized by an inflamed colon and severe watery diarrhea, in a nursing home and had a hell of a time recovering from it: The phantom doctor in charge of the facility’s residents didn’t treat it properly. This was late 2013. That Dad even acquired C. diff was an egregious lapse by this nursing home which, since his discharge, has been sold and reopened under a new name with new management. Good riddance.

In a study reported just last year, but based on 2011 data, the CDC found that one of every three C.-diff infections and two out of three “healthcare-associated” C.-diff infections occur in patients 65 years or older. (I prefer the description, healthcare-acquired, to healthcare-associated.) The CDC also concluded that more than 100,000 C.-difficile infections develop among residents of U.S. nursing homes each year.

Because of my father’s unfortunate experience, and how it blindsided me, I devote a lot of attention to C. diff in “Our Parents in Crisis.” I learned the hard way and am still learning. When Dad’s younger brother, my Uncle Pete, who has advanced lung cancer, became very ill with severe diarrhea last month after being treated for pneumonia in a small South Florida hospital and undergoing chemotherapy about 10 days after his discharge, my sister Britt and I immediately feared he had C. diff. By the time my 79-year-old uncle received a diagnosis in a bigger and better, but still small South Florida hospital (roughly 325 beds), he was septic. (See my 3/21/16 Facebook post on sepsis.)

Clostridium difficile, aka C. difficile, aka C. diff colitis, as I write in my book, “is a bacterial infection in the gut that causes at least three, but most often far more, bouts of nasty diarrhea a day and a host of other symptoms, depending on its severity, including nausea, abdominal cramping and pain, fever, and inflammation and swelling of the colon.

“In its worst form, the infection can lead to dehydration, kidney failure, and damage to the colon that can cause a rupture or a perforation, sepsis, and death. C. diff, which is shorthand for both the bacterium itself and the infection it causes, can kill anyone, but elders are more at risk than younger, healthier people.”

A C.-diff infection typically occurs in the colon of a patient who has recently taken antibiotics to clear up another infection, such as my uncle’s pneumonia. Antibiotics can wipe out healthy flora (microorganisms) that live harmlessly in the digestive tract and help to protect the body from infection, leaving a patient vulnerable when he or she is exposed to Clostridium difficile, typically in a hospital or a nursing home. C. diff takes advantage of the gut being out of microbial balance. The bacteria grow opportunistically, producing spores that release toxins that attack the colon’s lining. These toxins can be detected in a stool specimen, which is the means by which a diagnosis is obtained.

According to the CDC, 30 to 50 percent of the antibiotics prescribed in hospitals are “unnecessary or incorrect.” The U.S. public-health agency also estimates that more than 50 percent of the antibiotics prescribed in outpatient healthcare settings, such as doctors’ offices, typically for upper-respiratory infections (colds), are also unnecessary and ineffective. Of the half-million annual C.-diff infections reported by the CDC, more than 150,000 occurred in patients who had no documented in-patient healthcare exposure. They acquired C. diff in the community, a “never event” that underscores the need for better infection control and antibiotic use. (I explain never events in my book.)

As I report in “Our Parents in Crisis,” the antibiotics that lead most often to C. difficile are fluoroquinolones, cephalosporins, clindamycin, and penicillins. Shortly before he was exposed to the bacteria at the nursing home, my father took Augmentin®, which contains the penicillin, amoxicillin, and Keflex® , a broad-spectrum antibiotic that is a cephalosporin. When a person takes a broad-spectrum antibiotic, the CDC says, “beneficial bacteria that are normally present in the human gut and protect against infection can be suppressed for several weeks to months.”

I do not know what antibiotics my uncle received when he developed pneumonia in the first Florida hospital after being admitted for severe dehydration. My guess is a fluoroquinoline. He also may have received a broad-spectrum agent. I am confident, however, that he was exposed to C. diff in that hospital.

According to the CDC study, one out of every nine patients aged 65 or older with a healthcare-“associated” C.-difficile infection dies within 30 days of diagnosis, and more than 80 percent of the deaths associated with C. difficile occur among Americans 65 or older.

I was not happy about the antibiotic use that pre-dated my father’s infection, for reasons related to decisions made by his treating hospital physicians, but I, sadly, had no knowledge of C. difficile in 2013, just a general sense that infections spread in skilled nursing facilities. Ironically, after Dad’s diagnosis, which was delayed because the stool sample that the nursing home sent to a lab was somehow compromised, I began seeing newspaper articles everywhere about this bacterial scourge: A noxious strain of C. difficile had emerged and was infecting people who had not taken antibiotics, but had recently visited a healthcare clinic. Annual death totals due to C. diff had skyrocketed.

According to the CDC’s most recent survey on hospital-acquired infections, which I cite in my book, Clostridium difficile was the most common pathogen identified among 481 pathogens in 183 acute-care hospitals in 10 representative states. C. diff caused nearly 71 percent of all gastrointestinal infections suffered by patients and 12 percent of all hospital infections. Staphylococcus aureus, a major cause of pneumonia and surgical-site and bloodstream infections, came in second, accounting for nearly 11 percent of such infections. (See my 3/28/16 Facebook post about hospital infections and MRSA, methicillin-resistant Staphylococcus aureus.)

Clostridium difficile passes to humans by the fecal-oral route. People come in hand contact with contaminated human feces and then transmit the bacteria to their mouths when they don’t wash their hands thoroughly. They also may spread the bacteria to food, surfaces, and objects that they touch. In institutions, C. difficile spreads between patients mainly by hand-to-hand contact: from infected Patient #1-to-his nurse-to-vulnerable Patient #2, who puts his hand to his mouth.

My father was likely infected within a week of his admission to the nursing home. Despite his known recent antibiotic treatment and his debilitated condition, he was placed in a room in a wing of the facility that was known to be contaminated with C. diff. My mother, who was recovering from a broken leg in another wing, joined him there. That the SNF failed to ensure that its staff, especially its nurses, observed scrupulous infection-control measures, such as washing their hands and wearing protective disposable gowns and gloves, when dealing with infected patients made me furious.

After Dad was diagnosed and my parents’ room was tagged for infection control—and the family was on daily patrol—nurses still put their ungloved hands all over him. I walked in one time to find a nurse holding Dad’s hand tenderly in her uncovered hand.

Although it seems counter-intuitive, antibiotic therapy can cure C. difficile. For mild to moderate infections, physicians usually prescribe a 10-day course of oral Flagyl® (metronidazole), an antibiotic that the FDA has not approved for this use but has been shown to be effective. Unfortunately, Flagyl often causes nausea and leaves a bitter taste. The potent antibiotic, vancomycin, is typically prescribed in more severe and recurrent cases: Only the oral form is effective against C. diff.

A course of Flagyl seemed appropriate to the phantom nursing-home doctor in Dad’s mild-to-moderate case—or maybe that’s what this on-call professional ordered, perfunctorily, in all cases. The drug made Dad vomit, so he took an antiemetic in order to tolerate it. After only seven days of Flagyl, his GI symptoms subsided, and the head nurse terminated the therapy. But my father’s relief lasted just two to three days. The C.-diff returned.

(Note: Dad was now eating plain yogurt and taking probiotic supplements in an effort to introduce healthy bacteria into his GI tract that would outnumber and defeat the bad microbes.)

I argued with the head nurse for resumption of the antibiotic before the results of another stool culture came back, and for a full 10-day course, regardless of symptoms, and the doctor agreed to sign off on that. But this longer Flagyl course also didn’t eliminate Dad’s C.-diff infection.

Earlier, a therapeutic trial with liquid vancomycin had failed because Dad couldn’t keep it down. It wasn’t until after my father was discharged to a home setting where he could be isolated and I could arrange for private care that we learned from an emergency-medicine physician that he wouldn’t be cured until he took a two-week course of oral (by pill) vancomycin. This doctor had seen hundreds of cases, and he was right.

My C.-diff-infected Uncle Pete, who was in far worse shape than my father had been because of his cancer and other co-morbidities and his septic response to the GI infection, had been receiving intravenous Flagyl and oral vancomycin for about three days when his kidneys started to fail. He was about to become a CDC statistic when the hospital medical team decided to give him a fecal transplant, something that Britt and I had learned about during Dad’s ordeal.

Although usually performed for recurrent C. difficile colitis—typically after patients have had at least three recurrences of the C. diff infection and all drug therapies have failed—a fecal transplant delivers donor stool with a healthy diversity of bacteria into the diseased colon. The new bacteria reestablish the colonic microbial colony’s resistance to the C. difficile, an assertion of dominance, if you will. In the Georgetown Mini-Medical School lecture on gastroenterology that I attended last Tuesday (see my 4/6/16 Facebook post), Professor Thomas Sherman, Ph.D., described a fecal transplant as “re-poopulating” the colon.

I know this: It saved my uncle’s life.

After the fecal transplantation, which was performed via colonoscopy, Uncle Pete had to have days of dialysis to survive, but survive he did, and, gradually, he improved. (A transplant also can be done by nasoduodenal tube, but this method is less common.)

The known risks of fecal transplants are the same as those associated with colonoscopy, according to gastroenterologists who do these procedures. My uncle had no adverse effects. Amazingly, he was discharged to a nursing home just two weeks after the transplant, being free of infection and with his kidneys functioning on their own!

I asked the physician assistant of the gastroenterologist who did my uncle’s transplant, which consisted of commercially supplied stool ($1,000) from a carefully screened stranger-donor, not a family member, how often the specialist performed them and what their cure rate was. She said the hospital’s gastroenterologists do 20-25 transplants a year, and the procedures are 90-95% effective. Again, I was amazed, and grateful.

SOME REFERENCES:

Brandt, Lawrence, “Fecal Transplantation for the Treatment of Clostridium difficile Infection,” Gastroenterology & Hepatology (2012) 8: 191-94, at http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3365524/.

CDC, “Healthcare-Associated Infections (HAIs): Clostridium Difficile Infection,” and links therein, at http://www.cdc.gov/hai/organisms/cdiff/cdiff_infect.html.

CDC, “Nearly half a million Americans suffered from Clostridium difficile infections in a single year,” at http://www.cdc.gov/media/releases/2015/p0225-clostridium-difficile.html.

Mayo Clinic Staff, “C. Difficile Infections,” at http://www.mayoclinic.org/diseases-conditions/c-difficile/basics/treatment/com-20029664?p=1.

National Library of Medicine-NIH, “Clostridium Difficile Infections,” and citations therein, at https://www.nlm.nih.gov/medlineplus/clostridiumdifficileinfections.html.

Ann, 4/8/16

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